Folates comprise a class of water soluble vitamins that are essential for normal growth and maturation. Reduced folic acid co-enzymes are involved in one-carbon transfer reactions such as those necessary for the biosynthesis of methionine serine, deoxythymidylic acid, and purines. Little is known about the overall mechanism of cellular folate homeostasis. Knowledge about this process is an important health issue because of the increasing use of anti-folates in the treatment of neoplastic diseases, psoriasis, asthma to tissue cells is the folate receptor (also called the membrane folate binding protein). This proposal outlines three specific projects designed to study the molecular cytology of this receptor: a) determine how the folate receptor is coupled to transmembrane transport, which is required for delivery of folate to the cytoplasm; b) determine what tissues express the folate receptor in the adult as well as developing animal; c) understand how the folate receptor is synthesized, sorted and functions in polarized epithelial cells. These goals will be achieved by using contemporary cell and molecular biology techniques to study the behavior of this receptor in appropriate tissue culture cell systems as well as the adult and developing animal.